Introduction: α-Klotho (klotho) is a geroprotective protein inversely associated with coronary artery disease CAD and vascular aging. This study used intravascular ultrasound (IVUS) to study coronary artery plaque characteristics of patients with low circulating klotho. Hypothesis: Lower klotho is associated with vulnerable coronary artery plaque characteristics. Methods: Patients undergoing coronary angiogram for chest pain who had no CAD (<40% stenosis) underwent IVUS assessment. Images were obtained from the mid-LAD to the coronary ostium. Stored arterial plasma was used for α-klotho analysis by enzyme-linked immunosorbent assay. Results: A total of 58 consecutive patients were retrospectively studied. The median circulating klotho level of the cohort was 0.27 ng/mL [0.15; 1.24]. Patients with klotho less than the median were compared to those with levels greater than or equal to the median and were similar in age (53 ±11 vs. 56 ±10, p = 0.235) and sex distribution (86% vs. 76% female, p = 0.324). Patients with less klotho had higher coronary plaque burden (21.42% [17.185, 31.955] vs. 18.32 [10.5, 24.515], p=0.041) and larger plaque area (2.71 [2.03, 4.605] vs . 2.27 [1.41, 3.31] mm 3 /mm, p=0.058) compared to those with higher klotho. Lower klotho was associated with vulnerable plaque characteristics, including greater percentages of dense calcium (1.33% [0.265, 5.38] vs. 0.43% [0.015, 1.73], p=0.037) and necrotic core (5.43% [2.245, 10.5] vs. 2.22% [0.86, 4.50], p=0.011). Conclusions: Lower circulating klotho was associated with higher coronary plaque burden and vulnerable plaque characteristics. Klotho may be an early biomarker for risk in coronary artery disease.
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